Microbicides

ABSTRACT

When used in admixture with mancozeb, chlorothalonil, a copper salt, folpet, fluazinam or cymoxanil (it being possible for the latter to be used also together with one of the other five components), metalaxyl having a high R-enantiomer content of more than 70% by weight, or pure R-metalaxyl, exhibits a markedly increased fungicidal action against plant diseases as compared with a similar mixture in which metalaxyl is used in the form of the racemate.

This application is a DIV of Ser. No. 09/650,230 filed Aug. 29, 2000 nowU.S. Pat. No. 6,369,105 which is a DIV if Ser. No. 09/573,784 filed May17, 2000 now U.S. Pat. No. 6,248,762 which is a DIV of Ser. No.09/365,637 filed Aug. 3, 1999 now U.S. Pat. No. 6,087,388 which is a DIVof Ser. No. 09/150,435 filed Sep. 9, 1998 now U.S. Pat. No. 5,981,582which a DIV of Ser. No. 08/825,285 filed Mar. 27, 1997 now U.S. Pat. No.5,846,571 which is a DIV of Ser. No. 08/460,399 filed Jun. 2, 1995 nowU.S. Pat. No. 5,648,383.

The present invention relates to fungicidal two- and three-componentmixtures based on metalaxyl having an R-enantiomer content of more than70% by weight, and to the use thereof in controlling and preventingOomycetes infestation. The metalaxyl component is called activeingredient I.

The following fungicides may be used as the second component II of themixture:

IIA) mancozeb;

IIB) chlorothalonil;

IIC) a copper salt, for example CuCO₃, CuSO₄, Cu(OH)₂.CUCl₂, especiallyCu(OH)₂;

IID) folpet;

IIE) fluazinam[=3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitro-p-toluidine];and

IIF) cymoxanil, which can be used either on its own or in admixture withone of the above-mentioned components IIA to IIE (three-componentmixtures).

More specifically, the invention relates to mixtures comprisingmetalaxyl having an R-enantiomer content of more than 85% by weight,preferably of more than 92% by weight, and especially containing pureR-enantiomer that is substantially free of S-enantiomer.

Metalaxyl of the formula

has an asymmetric *C atom and can be resolved into the enantiomers incustomary manner (GB-P.1 500 581). Since 1975 it has been known to thoseskilled in the art that the R-enantiomer is far superior to theS-enantiomer in terms of fungicidal action and is in practice regardedas the true mechanism of action. Commercial metalaxyl is available inthe form of the racemate. Likewise, mixtures of metalaxyl racemate withmancozeb, chlorothalonil, copper preparations, folpet, fluazinam orcymoxanil have become known commercially or otherwise. There has in thepast never been any practical necessity to resolve the racemate, ofwhich half consists of the desired R-enantiomer.

It has now been found, completely surprisingly, that R-metalaxyl in pureor more than 70% form, in admixture with the fungicidal components IIAto IIF, achieves a synergistically enhanced action which in some casesexceeds that of the prior-known mixtures based on the racemate by afactor of 10. Given that half of the racemate consists of R-enantiomer,factors of approximately 2 or, at most, 3 were to be expected.

With this completely unexpected result, the present inventionconstitutes a very considerable enrichment of the art and represents apossible means of reducing in an environmentally protective manner thetotal amount of fungicides used for controlling Oomycetes on plants.

In addition to the two-component mixture I:II, the present inventionrelates also to a method of controlling fungi, which comprises treatinga site, for example a plant, that is infested by or threatened withinfestation by fungi with, in any desired sequence or simultaneously, a)component I and b) the active ingredient of formula II.

Advantageous mixing ratios of the two active ingredients are I:II=from10:1 to 1:100, preferably I:II=from 5:1 to 1:30. In many cases, mixturesin which the mixing ratio of the active substances I:II is from 1:1 to1:20, for example 2:5, 1:4, 1:8 or 1:10, are advantageous.

The active ingredient mixtures I+II according to the invention have veryadvantageous curative, preventive and systemic fungicidal properties forprotecting cultivated plants. The active ingredient mixtures of theinvention can be used to inhibit or destroy the micro-organisms whichoccur on plants or on parts of plants (the fruit, blossom, leaves,stems, tubers or roots) of different crops of useful plants, while atthe same time parts of plants that grow later are also protected againstsuch microorganisms. This applies especially also to microorganisms thathave developed reduced sensitivity to metalaxyl.

The active ingredient mixtures of formulae I and II are generally usedin the form of compositions. R-metalaxyl (formula I) and the activeingredient of formula II can be applied to the area or plant to betreated simultaneously or in immediate succession, if desired togetherwith further carriers, surfactants or other application-promotingadjuvants customarily employed in formulation technology.

Suitable carriers and adjuvants can be solid or liquid and are thesubstances ordinarily employed in formulation technology, e.g. naturalor regenerated mineral substances, solvents, dispersants, wettingagents, tackifiers, thickeners, binders or fertilisers.

A preferred method of applying an active ingredient mixture comprisingat least one of each of the active ingredients I and II is applicationto the parts of the plants that are above the soil, especially to theleaves (foliar application). The frequency and rate of applicationdepend upon the biological and climatic living conditions of thepathogen. The active ingredients can, however, also penetrate the plantthrough the roots via the soil (systemic action) if the locus of theplant is impregnated with a liquid formulation or if the substances areintroduced in solid form into the soil, e.g. in the form of granules(soil application).

The compounds of the combination are used in unmodified form or,preferably, together with the adjuvants conventionally employed informulation technology, and are therefore formulated in known mannere.g. into emulsifiable concentrates, coatable pastes, directly sprayableor dilutable solutions, dilute emulsions, wettable powders, solublepowders, dusts, granules, or by encapsulation in e.g. polymersubstances. As with the nature of the compositions, the methods ofapplication, such as spraying, atomising, dusting, scattering, coatingor pouring, are chosen in accordance with the intended objectives andthe prevailing circumstances. Advantageous rates of application of theactive ingredient mixture are normally from 50 g to 1800 g of activeingredient (a.i.) per hectare, preferably from 100 g to 1000 g a.i./ha.Mixtures of R-metalaxyl (I) with mancozeb (IIA) are advantageouslyemployed at rates of application of from 100 g to 120 g of I and 1600 gof IIA.

The formulations are prepared in known manner, e.g. by homogeneouslymixing and/or grinding the active ingredients with extenders, e.g.solvents, solid carriers and, where appropriate, surface-activecompounds (surfactants).

The agrochemical compositions generally comprise 0.1 to 99%, preferably0.1 to 95%, of active ingredients of formulae I and II, 99.9 to 1%,preferably 99.9 to 5%, of a solid or liquid adjuvant and 0 to 25%,preferably 0.1 to 25%, of a surfactant.

Whereas commercial products will preferably be formulated asconcentrates, the end user will normally employ dilute formulations.

Suitable target crops are especially potatoes, vines, hops, maize, sugarbeet, tobacco, vegetables (tomatoes, paprika, lettuce, etc.), and alsobananas, natural rubber plants, as well as lawn areas and ornamentals.Other plants threatened by downy mildew have become known inter aliafrom the literature relating to metalaxyl.

The Examples which follow serve to illustrate the invention, “activeingredient” denoting a mixture of R-metalaxyl and compound II in aspecific mixing ratio.

Wettable powders a) b) c) active ingredient 27% 51% 75% [I:IIA = 1:4(a),1:16(b), 2:13(c)] sodium lignosulfonate  5%  5% — sodium laurylsulfate 3% —  5% sodium diisobutylnaphthalene- —  6% 10% sulfonate octylphenolpolyethylene glycol —  2% — ether (7-8 mol of ethylene oxide) highlydispersed silicic acid  5% 10% 10% kaolin 60% 26% —

The active ingredient is thoroughly mixed with the adjuvants and themixture is thoroughly ground in a suitable mill, affording wettablepowders which can be diluted with water to give suspensions of thedesired concentration.

Emulsifiable concentrate active ingredient 10% (I:IIA, IIB, IID or IIE =3:7) octylphenol polyethylene glycol ether  3% (4-5 mol of ethyleneoxide) calcium dodecylbenzenesulfonate  3% castor oil polyglycol ether 4% (35 mol of ethylene oxide) cyclohexanone 30% xylene mixture 50%

Emulsions of any required dilution, which can be used in plantprotection, can be obtained from this concentrate by dilution withwater.

Extruder granules active ingredient (I:IIC = 1:4) 15% sodiumlignosulfonate  2% carboxymethylcellulose  1% kaolin 82%

The active ingredient is mixed and ground with the adjuvants, and themixture is moistened with water. The mixture is extruded and then driedin a stream of air.

Coated granules active ingredient (I:IID = 3:5)  8% polyethylene glycol(mol. wt. 200)  3% kaolin 89% (mol. wt. = molecular weight)

The finely ground active ingredient is uniformly applied, in a mixer, tothe kaolin moistened with polyethylene glycol. Non-dusty coated granulesare obtained in this manner.

Suspension concentrate active ingredient (I:IIF:IIA = 3:1:7) 44%propylene glycol 10% nonylphenol polyethylene glycol ether  6% (15 molof ethylene oxide) sodium lignosulfonate 10% carboxymethylcellulose  1%silicone oil (in the form of a 75%  1% aqueous emulsion) water 28%

The finely ground active ingredient is intimately mixed with theadjuvants, giving a suspension concentrate from which suspensions of anydesired dilution can be obtained by dilution with water. Such dilutionscan be used to treat living plants by spraying, pouring or immersion andto protect them against infestation by microorganisms.

BIOLOGICAL EXAMPLES

Fungicides have a synergistic effect whenever the fungicidal action ofthe active ingredient combination is greater than the sum of the actionsof the active ingredients when applied individually.

The action E to be expected for a given active ingredient combination,for example of two fungicides, obeys the so-called COLBY formula and canbe calculated as follows (COLBY, L. R. “Calculating synergistic andantagonistic responses of herbicide combinations”. Weeds 15, pages20-22, 1967) (LIMPEL et al., 1062 “Weeds control by . . . certaincombinations”. Proc. NEWCL, Vol. 16, pp. 48-53):

(mg a.i./liter=milligrams of active ingredient per liter or a multiplethereof)

X=% action by fungicide I at p mg a.i./liter

Y=% action by fungicide II at q mg a.i./liter

E=the expected action of fungicides I+II at a rate of application of p+qmg a.i./liter (additive action),

then according to Colby: $E = {X + Y - {\frac{X \cdot Y}{100}.}}$

If the action (O) actually observed is greater than the expected action,then the action of the combination is superadditive, i.e. there is asynergistic effect.

1) Action Against Plasmopara viticola on Vines

Small vine plants of the variety “Gutedel” are each grown in a plant-pot(diameter=6 cm) under greenhouse conditions and are sprayed in thetwo-leaf stage with an active ingredient mixture prepared from anemulsifiable concentrate. The following concentrations of activeingredient are each applied to four plants:

metalaxyl racemate: 2 mg and 6 mg a.i./liter;

R-metalaxyl (100%): 0.06 mg and 0.6 mg a.i./liter;

mancozeb: 2 mg and 6 mg a.i./liter.

These dilutions are prepared in demineralised water immediately beforethe leaves are sprayed. In order to eliminate the effect of the gasphase of the metalaxyl in the vicinity, all the plants are separatedfrom one another laterally by means of transparent plastics films andare kept in the dark for one day at 20-22° C. and about 100% relativehumidity.

The entire surface of the leaves of the plants is then uniformly sprayedto drip point with a freshly prepared sporangia suspension (120 000/ml)of a strain of Plasmopara viticola that is sensitive to metalaxyl. Theplants are then kept at 20-22° C. and about 100% relative humidity for 7days under artificial daylight of 16 hours' duration. Evaluation of theinfestation is then carried out. The Tables show in each case theaverage of four parallel sprayings. The expected action in the case ofmixtures is calculated according to COLBY.

Level of action of racemic metalaxyl and R-metalaxyl in admixture withresidual component mancozeb

E R-enantiomer Expected O Metalaxyl of metalaxyl Mancozeb Mixing actionObserved mg a.i./l mg a.i./l mg a.i./l ratio [COLBY] action 2 12 6 240.06 12 0.6 18 2 0 6 20 2 2 1:1 12 27 6 2 3:1 24 71 2 6 1:3 40 69 6 61:1 30 90 0.06 2  1:33 12 43 0.6 2 1:3 18 56 0.06 6  1:100 30 64 0.6 6 1:10 35 91

the action of 2 mg of racemic metalaxyl in admixture with 2 mg or 6 mgof mancozeb corresponds to that of 0.06 mg of R-metalaxyl in admixturewith 2 mg or 6 mg of mancozeb. This shows that the action is improvedabout 30-fold when the R-enantiomer is used instead of racemicmetalaxyl.

2) Action Against Phytophthora Infestans on Tomato Plants

Residual-protective Action

After a cultivation period of 3 weeks, tomato plants are sprayed with aseries of concentrations of a spray mixture prepared from anemulsifiable concentrate of the active ingredient mixture. The treatedplants are infected 48 hours later with a sporangia suspension of thefungus. Fungus infestation is evaluated after incubation of the infectedplants for 4 days at 90-100% relative humidity and 20° C.

The following results are obtained:

R-enantiomer Mancozeb Metalaxyl of metalaxyl Percent [ppm a.i.] [ppma.i.] [ppm a.i.] action 20 2 18  6   0.6  0 20 2 75  6   0.6  7 CopperR-enantiomer oxychloride Metalaxyl of metalaxyl Percent [ppm a.i.] [ppma.i.] [ppm a.i.] action 60 6 35 60 2   17.5 60 6 75 60 2 50

3) Action Against Phytophthora on Potato Plants

Residual-protective Action

After cultivation period of 3 weeks, 2- to 3-week-old potato plants(variety Bintje) are sprayed with a series of concentrations of a spraymixture prepared from an emulsifiable concentrate of the activeingredient mixture. The treated plants are infected 24 hours later witha sporangia suspension of the fungus. Fungus infestation is evaluatedafter incubation of the infected plants for 5 days at 90-100% relativehumidity and 20° C.

The following results are obtained:

R-enantiomer Mancozeb Metalaxyl of metalaxyl Percent [ppm a.i.] [ppma.i.] [ppm a.i.] action 20 2 70  6   0.6 15 20 2 100   6   0.6 50 CopperR-enantiomer oxychloride Metalaxyl of metalaxyl Percent [ppm a.i.] [ppma.i.] [ppm a.i.] action 60 6   17.5 60 2  0 60 6 70 60 2 35

Similarly markedly increased actions are achieved also with the othercomponents IIB, IID, IIE and IIF of the mixture.

Preferred mixing ratios (in amounts by weight) are:

R-metalaxyl(I):IIA (mancozeb)=1:1 to 1:20

I:IIB (chlorothalonil)=2:1 to 1:12

I:IIC (copper preparation)=5:1 to 1:30

I:IID (folpet)=3:1 to 1:10

I:IIE (fluazinam)=5:1 to 1:20

I:IIF (cymoxanil)=6:1 to 1:6

I:IIF:IIA=1 to 7:1:4 to 10

I:IIF:IID=1 to 7:1:2 to 8.

These marked increases in action with R-metalaxyl are observed alsoagainst other Oomycetes, especially Peronosporales, Pseudoperonospora,Albugo occidentalis, Phytophthora spp., Pythium, Bremia and otherpathogens.

What is claimed is:
 1. A fungicidal composition comprising fungicidallyeffective amounts of (I) metalaxyl, wherein more than 70% by weight ofthe metalaxyl is the R-enantiomer (IIF), cymoxanil, and a thirdcomponent (IIA) mancozeb, wherein the ratios by weight of I:IIF:IIA=1 to7:1:4 to 10, and an inert carrier is synergistic.
 2. A composition ofclaim 1, wherein the metalaxyl has an R-enantiomer content of more than85% by weight.
 3. A composition of claim 1, wherein the metalaxyl has anR-enantiomer content of more than 92% by weight.
 4. A composition ofclaim 1, wherein the metalaxyl is substantially free of theS-enantiomer.
 5. A method of controlling and preventing Oomycetesinfestation in plants, parts of plants, or at the site of their growth,which comprises applying thereto a synergistic, fungicidally effectiveamounts in any desired sequence, simultaneously or in immediatesuccession, (I) metalaxyl, wherein more than 70% by weight is theR-enantiomer, (IIF) cymoxanil, and a third component (IIA) mancozeb,wherein the ratios by weight of I:IIF:IIA=1 to 7:1:1 to
 10. 6. A methodof claim 5, wherein the metalaxyl has an R-enantiomer content of morethan 85% by weight.
 7. A method of claim 5, wherein the metalaxyl has anR-enantiomer content of more than 92% by weight.
 8. A method of claim 5,wherein the R-metalaxyl is substantially free of the S-enantiomer.
 9. Amethod of claim 5, wherein the plants are selected from Phytophthoraspp., Plasmopara, Pythium, Pseudoperonospora, Albugo occidentials, andBremia.
 10. A fungicidal composition comprising fungicidally effectiveamounts of (I) metalaxyl, wherein more than 70% by weight of themetalaxyl is the R-enantiomer (IIF), cymoxanil, and a third component(IID) folpet, wherein the ratios by weight of I:IIF:IID=1 to 7:1:2 to 8,and an inert carrier is synergistic.
 11. A composition of claim 10,wherein the metalaxyl has an R-enantiomer content of more than 85% byweight.
 12. A composition of claim 10, wherein the metalaxyl has anR-enantiomer content of more than 92% by weight.
 13. A composition ofclaim 10, wherein the metalaxyl is substantially free of theS-enantiomer.
 14. A method of controlling and preventing Oomycetesinfestation in plants, parts of plants, or at the site of their growth,which comprises applying thereto a synergistic, fungicidally effectiveamounts in any desired sequence, simultaneously or in immediatesuccession, (I) metalaxyl, wherein more than 70% by weight is theR-enantiomer, (IFF) cymoxanil, and a third component (IID) folpet,wherein the ratios by weight of I:IIF:IID=1 to 7:1:2 to
 8. 15. A methodof claim 14, wherein the metalaxyl has an R-enantiomer content of morethan 85% by weight.
 16. A method of claim 14, wherein the metalaxyl hasan R-enantiomer content of more than 92% by weight.
 17. A method ofclaim 14, wherein the R-metalaxyl is substantially free of theS-enantiomer.
 18. A method of claim 14, wherein the plants are selectedfrom Phytophthora spp., Plasmopara, Pythium, Pseudoperonospora, Albugooccidentials, and Bremia.